Apparatus and Method for Generating an Aerosol

ABSTRACT

The present invention is directed to improvements related to the generation of aerosols and outlines an apparatus and methods which supports deagglomeration and counteracts reagglomeration of aerosol particles. The apparatus is provided with an arrangement of inlet conduits for pressurized gas that promote transportation with a rotational flow towards an exit conduit. In order to further support production of high quality aerosols, the apparatus can be provided with an impactor aligned with the exit conduit with at least one impacting surface that minimizes formation of impact residues.

FIELD OF THE INVENTION

The present invention is directed to improvements related to thegeneration of aerosols and outlines devices and methods which supportdeagglomeration and counteract reagglomeration of aerosol particles.

BACKGROUND OF THE INVENTION

European patent specification EP 1 028 815 describes an apparatus thateffectively generates batches of high quality aerosols from dry powder.Such aerosols can be received in a vertically connected holding chamberand transported to a target, as exemplified in WO 2009/002267.

The apparatus of EP 1 028 815 operates by using the energy in acompressed gas to break up the powder in a powder chamber where thepowder is instantaneously pressurized and suspended, whereupon aturbulent non-rotating flow transports the powder for ejection through anarrow exit conduit leading to the holding chamber. The rapid expansionfrom the narrow exit conduit accomplishes deagglomeration and generationof a micrometer size aerosol with a controlled, narrow sizedistribution. Even if this technology gives excellent results for abroad range of powder qualities, there are certain powder materialswhich are exceedingly cohesive due to mechanisms like van der Waalforces, electrostatic interaction and capillary condensation of humidityin hygroscopic material. Apart from impaired control of the aerosolparticle size distribution this may lead to immediate problems in theprocess from clogging and material losses. The present invention aims atimproving the discussed technology of aerosolization by boosting thede-agglomeration of aerosolized powders.

US 2009/0191349 discloses an aerosol generator wherein the powderaccommodated in a generator vessel with a number of differently directedjetting ports that stationary deaggregates and fluidizes the powder. Inorder to generate a transported aerosol, a supply gas introduced frombelow a porous pate to transport an aerosol with classified particles toan outlet. US 2009/0260623 discloses a hand held aerosol generator witha rotating powder capsule and a number of angled air inlet ports foraerosol generation by the user. U.S. Pat. No. 6,415,790 disclosesanother hand held aerosol generator wherein powder released fromspecifically designed blisters are transported to the inhaling user byturbulence from air inlet channels. None of these documents provide anyparticular means for counteracting particles of the generated aerosol toagglomerate. WO 02/056948 discloses and inhaler with an aerosolgenerator and an impact member with flat round surface surrounded by aconical surface facing the aerosol stream. Even if the impact memberpromotes deagglomeration, its position and construction may riskaccumulation of adhesive powder particles in the region of the flat apexof the impactor member.

It is evident that there is a need for an aerosol generator that isadapted also for powders with adhesive particles with high tendency toagglomerate that is capable of effectively transporting the aerosolwhile promoting deagglomeration in order to provide aerosols withimproved better controlled particle size and thereby obtain improveddose accuracy for inhalable aerosolized products.

DESCRIPTION OF THE INVENTION

In general terms, the present invention is directed to an apparatus anda method of generating aerosol doses from a dry powder source with ahighly pressurized gas and thereby provide means that improve aerosolquality and the load capacity also from powders with a strongcohesiveness and a great ability to withstand deagglomeration.

The present invention is directed to an aerosol generating apparatuscomprising an at least partially spherical powder chamber for loadingand mixing powder with pressurized gas, having one or severalcompartments, at least two pressure conduits operably connected to apressure chamber for introducing pressurized gas to the powder chamberby at least two inlet orifices and an ejection conduit opening at anexit orifice to ambient pressure. The apparatus is further characterizedin that it has a main axis of rotational symmetry, in that the at leasttwo inlet conduits have each a symmetry axis extending into projectionlines and are arranged to admit inlet flows in opposite directions, inthat the inlet conduit projection lines are equidistant to a planeintersecting the apparatus main axis of symmetry termed the inletconduit parallel plane, and in that the inlet conduit projection linesform acute angles with a normal plane to the inlet conduit parallelplane, termed the inlet conduit normal plane. In one aspect the acuteangles are in the approximate range of 35 to 70 degrees and the acuteangles can have the same or different values. In accordance with theinvention, the at least two inlet orifices are admitted to introducepressurized gas “off-set” to the apparatus main axis of symmetry, inopposite directions, so a powerful rotating flow towards the exitconduit will become established. The apparatus is further characterizedin that the at least two inlet conduits have inlet orifices located theat least partially spherical part of the powder chamber. In the contextof the present invention the term “at least partially” spherical has themeaning of a full sphere or any fraction of a sphere, such as ahemisphere,

In one aspect, the powder chamber comprises an essentially sphericalcompartment comprising at least two inlet orifices for pressurized gas.

In accordance with one aspect the invention, the apparatus can be loadedbatch-wise with aerosolizable powder. According to another aspect, theapparatus can be provided with arrangements that admit a plurality ofdiscreet powder compositions to be aerosolized, simultaneously and/orsequentially. As an example the powder compositions can arranged indisplaceable blisters packages and similar multi-compartment containers.

In one aspect the powder chamber comprises an essentially hemisphericalcompartment comprising at least two inlet orifices for pressurized gas.

In one aspect, the powder chamber comprises a substantially cylindricalcompartment, a substantially ellipsoid compartment and the ellipsoidcompartment comprises the ejecting conduit. By way of an advantageousexample, the apparatus can comprise a hemispherical part arranged withthe at least two inlet conduits, a cylindrical midsection and anellipsoidal upper section with the exit conduit.

In one aspect of the invention, the apparatus has a minimum distancebetween the inlet conduit projection lines and the inlet conduitparallel plane that is from about 0.01 to about 1 mm.

In one aspect, the apparatus is provided with an ejecting conduit havingan abrupt inlet. The ejecting conduit can have a substantially uniformcross-section, essentially shaped as a cylinder. The definition of anabrupt inlet is further outlined in European patent specification1028815.

In one aspect, the apparatus is provided with at least two inletconduits which are essentially cylindrical and the inlet orifice isconfigured as an ellipsoid.

The apparatus according to the different aspects of the invention canfurther at least one additional inlet conduit with a projection linethat intersects the inlet conduit parallel plane.

In one further aspect, the invention relates to an aerosol generatingapparatus comprising a powder chamber for loading and mixing powder withpressurized gas, at least two pressure conduits operably connected to apressure chamber for introducing pressurized gas to the powder chamberby at least two inlet orifices and an ejection conduit opening at anexit orifice to ambient pressure. The ejection conduit preferably has anabrupt inlet as defined in European patent specification 1028815 and atleast two inlet conduits may be arranged with the previously definedoff-set arrangement and other described definitions. According to thisaspect, the apparatus comprises an impactor adapted to meet the powderdischarged from the exit orifice, by being aligned with the ejectionconduit in an impactor housing. Further according to this aspect, theimpactor comprises an impactor body having an impacting surface andbetween the impactor body and an impactor housing, an impactor channelor slit is provided with a substantially ring-shaped shapedcross-section. Still further according to this aspect, the impactor bodycomprises a conical part wherein said conical part provides a primaryimpacting surface and a substantially cylindrical part. The impactorbody is accommodated in an impactor housing and arranged so that theannular axially extended channel or slit is provided between theimpactor body and the impactor housing. The entrance region of theannular axially extended slit comprises a secondary impaction surface.The secondary impact surface is provided at the cylindrical innersurface of the cylindrical part of the impactor housing. The housing isdimensioned and arranged to receive the aerosol delivered from ejectionorifice in a manner that counteracts pile-up of material and securesexposure to the impacting surface. The annular slit is thus arranged tocomprise both a secondary impacting surface and to retard the aerosolflow in order to contribute to an additional break-up of agglomerates.In one aspect, the conical part of the impactor body is a recessed conecomprising a surface with a tangent having an angle with the main axisof symmetry that increases with the cone radius, admitting essentiallythe same acute impact angle for each powder agglomerate meeting theimpacting surface. The so curved impactor surface provides for avoidingimpact angles close to perpendicularly in order to avoid impact residuesof material to form and accumulate and thereby potentially decreasedeagglomeration capacity of the apparatus. By means of the curvedimpactor surface and the narrow annular slit deagglomeration isperformed in two stages and at different sites of the impactor whichcontribute to significant improvements in counteracting reagglomerationand provide for a controlled aerosol particle size also for particleswith adhesive characteristics. For this reason, it is advantageous thatthe slit is designed with suitable width considering both desirableaerosol exit velocity and complementary impacting effect whencounteracting deagglomeration. In one aspect the slit has width of 0.2mm or less such 0.2 mm, 0.1 mm, 0.15 mm, or 0.005 mm.

In another aspect, the invention relates to a method of generating anaerosol. The method comprises the steps of loading a powder chamber withan aerosolizable powder; releasing a pressurized gas and introducing itinto an at least partially spherical part of the powder chamber by atleast two pressure conduits with inlet orifices and providing asuspension of mixed gas and powder; establishing a rotating flow of thesuspension in at least one compartment of said powder chamber; admittingthe flow of the suspension to establish along the powder chamber innerwalls to an ejection conduit of the powder chamber; admitting thesuspension to form an aerosol in an ejection nozzle and subjecting it toat least one impacting surface and transporting it to through asubstantially ring-shaped impactor channel; and providing and optionallycollecting the so formed aerosol.

In one aspect of the method the pressurized gas has a pressure of atleast 50 bar, for example about 100 bar. The pressurized gas will thenbe able to become introduced at a sonic velocity and by arranging atleast two inlet conduits according to what has been defined above, apowerful rotating flow of suspension powder in gas can be established.In one aspect, the rotating flow is established in at least asubstantially hemispherical compartment of the powder chamber.

In one aspect of the method, the aerosol particles meet a primaryimpactor surface at essentially the same impact angle in order tominimize the risk of obtaining impact residues on the surface.

In one aspect of the method, subsequent to the first impacting surface,the stream of aerosol particles meet a secondary impacting surface at anessentially non-perpendicular angle. In this aspect the primary andsecondary surfaces are defined according to the previous parts of thespecification.

The invention according to the described aspects has by providing a feedof the loaded powder with a rotating flow towards the exit conduit, twomajor advantages: I) The more gradual feed of material induced by therotation substantially decrease the risk of clogging the exit conduit atthe narrowest part. II) The more gradual feed of material toward animpactor surface in the exit conduit decreases, the risk of agglomeratesimpacting on each other rather than on the hard impactor surface. Thisincreases the load capacity of the aerosol generator at a maintainedaerosolizing ability.

DETAILED DESCRIPTION OF THE INVENTION Short Description of Drawings

FIG. 1 shows an aerosol generator according to the invention through asection representing a plane of symmetry with the inlet orifices forpressurized gas schematically shown.

FIG. 2 shows the aerosol generator with the inlet orifices as viewedthrough plane A-A′ in FIG. 1. Also indicated are the inlet conduitparallel plane B-B′ and its normal plane C-C′.

FIG. 3 shows a section of the apparatus, wherein the inlet conduitparallel plane B-B″ is the plane of the paper demonstrating how aschematically shown inlet conduit projection line (shown in FIG. 2) hasan angle α to the normal plane C-C′.

FIG. 4 shows the impactor and is housing in an enlargement of thearrangement of FIG. 1.

Before the invention is disclosed and described in detail, it is to beunderstood that this invention is not limited to particular compounds,configurations, method steps, substrates, and materials disclosed hereinas such compounds, configurations, method steps, substrates, andmaterials may vary somewhat.

It is also to be understood that the terminology employed herein is usedfor the purpose of describing particular embodiments only and is notintended to be limiting since the scope of the present invention islimited only by the appended claims and equivalents thereof.

If nothing else is defined, any terms and scientific terminology usedherein are intended to have the meanings commonly understood by thoseskilled in the art to which this invention pertains.

It must be noted that, as used in this specification and the appendedclaims, the singular forms “a”, “an” and “the” include plural referentsunless the context clearly dictates otherwise.

The term “about” as used in connection with a numerical value throughoutthe description and the claims denotes an interval of accuracy, familiarand acceptable to a person skilled in the art. Said interval is ±10%.

Other features and uses of the invention and their associated advantageswill be evident to a person skilled in the art upon reading thedescription and the examples.

It is to be understood that this invention is not limited to theparticular embodiments shown here. The following examples are providedfor illustrative purposes and are not intended to limit the scope of theinvention since the scope of the present invention is limited only bythe appended claims and equivalents thereof.

The following definitions include terms used in the detailed descriptionof the invention, but are also valid for the same terms in any earliergeneral description of the invention and the appended claims. Certainterms are also defined in the general, earlier contexts of thedescription.

A powder chamber is the chamber set to accommodate the powder to beaerosolized. The powder camber be essentially spherical or have othersymmetrical shapes.

An inlet conduit is a conduit for transporting pressurized gas to thepowder chamber and may include one or more releasable valves to bereleased when charging the apparatus. The inlet conduit or conduitsterminate with an inlet orifice to the powder chamber.

An ejection conduit is an exit conduit of the powder chamber fordischarging the mixture of powder and pressurized air from the powderchamber. The ejection conduit terminates with an ejection orifice toambient air.

The main axis of rotational symmetry of the apparatus is the axis ofsymmetry the apparatus through the exit nozzle of the apparatus. Aninfinite number of symmetry planes can be defined to be aligned with therotational axis of symmetry and intersecting each other at arbitraryangles.

An inlet conduit projection line coincides with the axial symmetry lineof the essentially cylindrical inlet conduit extends from inlet orificeinto the powder chamber. Inlet conduit projection lines of the at leasttwo inlet orifices are equidistant to a plane intersecting the main axisof rotational symmetry of the apparatus termed inlet conduit parallelplane.

Off-set distance is the distance between the inlet conduit projectionlines and the inlet conduit parallel plane. The off-set distance is >0.The projection lines of at least two inlet orifices for pressurized gasare off-set from the main axis of rotational symmetry. Accordingly, theprojection lines of further, additional inlet orifices may lie withinone single plane of symmetry and intersect the projection line throughthe exit orifice.

An acute angle is an angle less than about 70 degrees, preferable lessthan 60 degrees. An acute angle is formed between the inlet conduitprojection lines and a normal plane to the inlet conduit parallel plane.

An impact angle is the angle between the path of aerosol particle or anagglomerate of aerosol particle travelling from the ejection orifice andonto the impactor surface.

FIG. 1 shows the apparatus 10 in a section according to a symmetry planewith a main axis of rotational symmetry 28. The powder chamber 12 has ahemispherical part 12B, a cylindrical part 12B and an ellipsoidal part12C. The apparatus can be accommodated in housing or a similararrangement. In FIG. 1 the two inlet conduits 18A and 18B and theirorifices are only schematically shown and it is referred to FIG. 2 thatis a view from above from section A-A′ in FIG. 1 for their arrangements.FIG. 1 further schematically shows the ejection conduit 20 with itsejection orifice and the impactor arrangement 30. The impactorarrangement 30 comprises an impactor body 32, a ring shaped impactorchannel 36 providing an annular slit surrounding the impactor body 32.The impactor body 32 is provided with a cylindrical part and a conicalpart that will be described in more detail in the context of FIG. 4.FIG. 1 further illustrates the rotating flow established by thepressurized gas from the inlet conduits and how a flow is establishedforwards along the powder chamber inner walls towards the ejectionconduit.

The view from above along section A-A′ in FIG. 1 is shown in FIG. 2 anddemonstrates two oppositely arranged inlet conduits with inlet orificesto the powder chamber. FIG. 2 further shows inlet conduit projectionlines 18A′ and 18B′, respectively which have the same distance to theinlet conduit parallel plane B-B′. This distance is between 0.01 to 1mm. The inlet conduit parallel plane B-B′ has a normal plane C-C′ termedinlet conduit normal plane. The inlet conduits are cylindricallyarranged and the inlet orifices are ellipsoidal with a largest dimensionof in the range of about 0.5 to 1 mm. The exit orifice has a diameter inthe range about 0.2 to 1 mm, in a powder chamber volume of about 1 ml.FIG. 2 also demonstrates the opposite direction of the inlet flows ofpressurized gas.

FIG. 3 further illustrates the angular arrangement of the inletconduits, In FIG. 3 one inlet conduit projection line from inlet conduit18B is depicted to form the acute angle α with the inlet conduit normalplane (C-C′ in FIG. 2) that has a value in the range of 35-65 degrees.The other inlet orifice can be depicted in the same manner with an acuteangle β. These angles can have the same or different acute values.

FIG. 4 is a detailed view of the impactor 30 in FIG. 1, showing theimpactor accommodated in the impactor housing. The annular slit 36surrounding the impactor body 32 has width of about of about 0.1 to 0.2mm and the cylindrical part of the impactor body has diameter of 3-4 mm.The annular slit length is 2-3 mm. FIG. 4 further demonstrates therecessed cone of the impactor body with its curved primary impactingsurface 34. It is schematically shown how agglomerates travel from theejection conduit of the powder chamber and that the curvature of theimpacting surface admits that a substantially constant acute impactingangle γ is maintained irrespectively of where the impacting surface ishit. It is also schematically shown how the tangent to the surface hasan angle with the main axis of symmetry that increases with the coneradius of the recessed cone. The so arranged primary impacting surface34 will counteract formation of impact residues which may form whenagglomerates hit the primary impacting surface 34 perpendicularly orclose thereto. The impactor housing 38 is dimensioned to counteract pileup of aerosolized material and is formed to admit the annular slit 36 toextend between the cylindrical part of the impactor body and to providean inner surface of the cylindrical part of the impactor housing 38. Asecondary impacting surface 40 is formed at the inner surface of thecylindrical part of the impactor housing in region of the entrance ofthe annular slit. In operation, powder (aerosol particles) will departessentially tangentially from the primary impacting surface and hit thesecondary impacting surface at an essentially non-perpendicularimpacting angle. The aerosol flow rate will retard in the annular slitand the aerosol will be distributed form the impactor orifice as awell-defined aerosol plume. The described impactor with itscomplementary impacting surfaces provides a very efficient way ofproducing homogenous and well-defined aerosols arriving in a plume shapefrom the slit. It has been found that powders that have been regarded asdifficult to handle by forming needle shaped crystals efficiently can bebroken up by the apparatus according to the invention.

1.-20. (canceled)
 21. An aerosol generating apparatus comprising an atleast partially spherical powder chamber for loading and mixing powderwith pressurized gas having one or several compartments; at least twoinlet conduits operably connected to a pressure chamber for introducingat inlet orifices pressurized gas to the powder chamber by at least twoinlet orifices; and an ejection conduit opening at an exit orifice toambient pressure, wherein (i) the apparatus has a main axis ofrotational symmetry; (ii) the at least two inlet conduits have each asymmetry axis extending into projection lines and are arranged to admitinlet flows in opposite directions; (iii) the inlet conduit projectionlines are equidistant to a plane intersecting the apparatus main axis ofsymmetry termed inlet conduit parallel plane; (iv) the inlet conduitprojection lines form acute angles with a normal plane to the inletconduit parallel plane, termed the inlet conduit normal plane; and (v)the at least two inlet conduits have inlet orifices located in the atleast partially spherical part of the powder chamber.
 22. The apparatusaccording to claim 21 wherein the powder chamber comprises anessentially hemispherical compartment, comprising the at least two inletorifices for pressurized gas, and wherein the distance between saidinlet orifices is equal or slightly less than the diameter.
 23. Theapparatus according to claim 21, wherein the powder chamber is sphericaland wherein the distance between said inlet orifices is equal orslightly less than the diameter.
 24. The apparatus according to claim21, wherein the powder chamber comprises an essentially cylindricalcompartment and an essentially ellipsoid compartment.
 25. The apparatusaccording to claim 24, wherein the ellipsoid compartment comprises theejecting conduit.
 26. The apparatus according to claim 21, wherein thedistance between the conduit projection line and of inlet conduitparallel plane is from about 0.01 to about 1 mm.
 27. The apparatusaccording to claim 21, wherein the ejection conduit has an abrupt inlet.28. The apparatus according to claim 21, wherein the ejection conduithas a substantially uniform cross-section, essentially shaped as acylinder.
 29. The apparatus according to of claim 21, comprising animpactor adapted to meet the powder discharged from the exit nozzle. 30.The apparatus according to claim 29, wherein the impactor comprises animpactor body having an impacting surface and between the impactor bodyand an impactor housing an impactor channel is provided with asubstantially ring-shaped shaped cross-section.
 31. The apparatusaccording to claim 21, wherein the inlet conduit is essentiallycylindrical and the inlet orifice is configured as an ellipsoid.
 32. Theapparatus according to claim 30, wherein the impactor body comprises asubstantially cylindrical part and a conical part and wherein saidconical part provides a primary impacting surface.
 33. The apparatusaccording to claim 32, wherein the impactor further comprises asecondary impacting surface provided at the cylindrical inner surface ofthe a cylindrical part of the impactor housing at the entrance of theannular impactor channel.
 34. The apparatus according to claim 32,wherein the conical part is a recessed cone comprising a surface with atangent having an angle with the main axis of symmetry increasing withthe cone radius, admitting essentially the same acute impact angle γ foreach powder agglomerate meeting the impacting surface.
 35. The apparatusaccording to any claim 21, comprising at least one additional inletconduit with a projection line that intersects the inlet conduitparallel plane.
 36. A method of generating an aerosol comprising thesteps of: (i) loading an at least partially spherical powder chamberwith an aerosolizable powder; (ii) releasing a pressurized gas andintroducing it into the powder chamber by at least two pressure conduitsentering by inlet orifices in the at least partially spherical part ofthe powder chamber and providing a suspension of mixed gas and powder;(iii) establishing a rotating flow of the suspension in at least onecompartment of said powder chamber; (iv) admitting a flow of thesuspension to establish along the powder chamber inner walls to anejection conduit of the powder chamber; (v) admitting the suspension toform an aerosol in an ejection nozzle and subjecting it to at least oneimpacting surface and transporting it to through a substantiallyring-shaped impactor channel; and (vi) providing and optionallycollecting the so formed aerosol.
 37. The method according to claim 36,wherein the pressurized gas has a pressure of at least 50 bar.
 38. Themethod according to claim 36, wherein the rotating flow is establishedin a substantially hemispherical compartment of the powder chamber. 39.The method according to any one of claims 36, wherein the aerosolparticles meet a primary impacting surface at essentially the same acuteimpact angle.
 40. The method according to claim 39, wherein the aerosolparticles subsequent to the primary impacting surface meet a secondaryimpacting surface at an essentially non-perpendicular angle.